title: Common variants in the BCL9 gene conferring risk of schizophrenia.
abstract: BACKGROUND
  Recent genome-wide association studies have revealed that common variations and rare copy-number variations contribute to the risk of mental disorders. Rare recurrent microdeletions at 1q21.1 were reported to be associated with schizophrenia, and the BCL9 gene at 1q21.1 was also a functional candidate gene for mental disorders.
  
  
  OBJECTIVE
  To investigate and validate whether common variations exist in a functional candidate gene in the copy-number variation region, and, if so, to determine whether these variations confer risk of schizophrenia or other mental disorders.
  
  
  METHODS
  A 3-stage case-control study.
  
  
  METHODS
  Shanghai, China.
  
  
  METHODS
  A total of 12 229 subjects were included: 5772 normal controls, 4187 patients with schizophrenia, 1135 patients with bipolar disorder patients, and 1135 patients with major depressive disorder. Main Outcome Measure During the first and second stages of our study, we genotyped 10 single-nucleotide polymorphisms using the ligation detection reaction method. During the third stage of our study, all single-nucleotide polymorphisms were genotyped using TaqMan technology (Applied Biosystems, Foster City, California).
  
  
  RESULTS
  During the first stage of our study, we found that rs672607 was significantly associated with schizophrenia (P = 2.69 × 10(-5)). During the second stage, rs672607 was successfully replicated (P = 1.33 × 10(-5)), and rs9326555 (P = .002), rs1240083 (P = 1.7 × 10(-4)), and rs688325 (P = .006) were newly identified to be significant. During the third stage, we genotyped all single-nucleotide polymorphisms in 1135 patients with schizophrenia, 1135 patients with bipolar disorder, 1135 patients with major depressive disorder, and 1135 normal controls for further validation. Finally, when we combined all the data from the 3 stages of our schizophrenia study, we found that rs9326555 (P = 1.53 × 10(-5)), rs10494251 (P = .02), rs1240083 (P = 1.52 × 10(-4)), rs672607 (P = 1.23 × 10(-11)), rs688325 (P = 2.54 × 10(-4)), and rs3766512 (P = .01) were significant. Moreover, we found that rs672607 was significant in major depressive disorder (P = .001) and bipolar disorder (P = .03), and rs10494251 (P = .04), rs1541187 (P = .04), rs688325 (P = .02), and rs946903 (P = .006) were significant in major depressive disorder.
  
  
  CONCLUSIONS
  These findings indicate that common variations in the BCL9 gene confer risk of schizophrenia and may also be associated with bipolar disorder and major depressive disorder in the Chinese Han population.
authors.affiliation: Bio-X Center and Affiliated Changning Mental Health Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, China.
authors.forename: Junyan
authors.initials: J
authors.lastname: Li
authors.forename: Guoquan
authors.initials: G
authors.lastname: Zhou
authors.forename: Weidong
authors.initials: W
authors.lastname: Ji
authors.forename: Guoyin
authors.initials: G
authors.lastname: Feng
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhao
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: You
authors.initials: Y
authors.lastname: Li
authors.forename: Peng
authors.initials: P
authors.lastname: Chen
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zeng
authors.forename: Ti
authors.initials: T
authors.lastname: Wang
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Hu
authors.forename: Linqing
authors.initials: L
authors.lastname: Zheng
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Shen
authors.forename: Lin
authors.initials: L
authors.lastname: He
authors.forename: Yongyong
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People; D001714:Bipolar Disorder / Q000235:genetics; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D056915:DNA Copy Number Variations; D003865:Major Depressive Disorder / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics*; D014157:Transcription Factors
chemical_list: C111180:BCL9 protein, human; D009363:Neoplasm Proteins; D014157:Transcription Factors